Design and Endpoints for Clinical Trials in Primary Sclerosing Cholangitis

Cyriel Y. Ponsioen, Keith D. Lindor, Ruby Mehta, Lara Dimick‐Santos – 25 March 2018 – Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for which there is no effective therapy. Interest has grown in developing treatments for this condition, with several agents proposed as potential therapies. However, there is a lack of clarity about how to measure clinical benefit in trials involving patients with this complex and rare disease.

Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas

Jean‐Charles Nault, Gabrielle Couchy, Stefano Caruso, Léa Meunier, Laure Caruana, Eric Letouzé, Sandra Rebouissou, Valérie Paradis, Julien Calderaro, Jessica Zucman‐Rossi – 24 March 2018 – Genetic alterations define different molecular subclasses of hepatocellular adenoma (HCA) linked with risk factors, histology and clinical behavior. Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess the significance of ASS1 expression through the scope of the HCA molecular classification.

Nicotinamide adenine dinucleotide phosphate (reduced) oxidase 2 modulates inflammatory vigor during nonalcoholic fatty liver disease progression in mice

Rajib Mukherjee, Maria E. Moreno‐Fernandez, Daniel A. Giles, Monica Cappelletti, Traci E. Stankiewicz, Calvin C. Chan, Senad Divanovic – 24 March 2018 – Nonalcoholic fatty liver disease (NAFLD) represents a disease spectrum ranging from benign steatosis to life‐threatening cirrhosis and hepatocellular carcinoma. Elevated levels of reactive oxygen species (ROS) and exacerbated inflammatory responses have been implicated in NAFLD progression.

Na+‐taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice

Davor Slijepcevic, Reinout L.P. Roscam Abbing, Claudia D. Fuchs, Lizette C.M. Haazen, Ulrich Beuers, Michael Trauner, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf – 24 March 2018 – Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na+‐Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of BSs, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury.

Ubiquitin‐Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice

Yichao Zhao, Fang Wang, Lingchen Gao, Longwei Xu, Renyang Tong, Nan Lin, Yuanyuan Su, Yang Yan, Yu Gao, Jie He, Lingcong Kong, Ancai Yuan, Ying Zhuge, Jun Pu – 23 March 2018 – Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis (HS), insulin resistance (IR), and inflammation, poses a high risk of cardiometabolic disorders. Ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme, is pivotally involved in regulating multiple inflammatory pathways; however, the role of USP4 in NAFLD is unknown.

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